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DOI: 10.1055/s-2006-947354
Remarkably Chemoselective Reduction of Unmodified Baylis-Hillman Adducts by InCl3/NaBH4: Application to the Stereoselective Synthesis of Trisubstituted Alkenones Including Two Alarm Pheromones [1]
Publication History
Publication Date:
24 July 2006 (online)

Abstract
A novel, convenient and solely stereoselective synthesis of trisubstituted E-alkenones has been achieved by InCl3/NaBH4 mediated chemoselective reduction of unmodified Baylis-Hillman adducts derived from vinyl ketones and cycloalkenones for the first time. The efficiency of this methodology in the practical synthesis of (S)-(+)-manicone and (S)-(+)-normanicone, two alarm pheromones of Manica ants, has been demonstrated.
Key words
unmodified Baylis-Hillman adduct - chemoselectivity - stereoselectivity - α,β-unsaturated ketones - insects’ pheromones
IICT communication No. 060622. Part 80 in the series ‘Studies on Novel Synthetic Methodologies’.
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References and Notes
IICT communication No. 060622. Part 80 in the series ‘Studies on Novel Synthetic Methodologies’.
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General Procedure for the Reduction of Adducts.
To a stirred solution of InCl3 (90 mg, 0.4 mmol) and NaBH4 (168 mg, 4.5 mmol) in dry MeCN (10 mL) was added a solution of Baylis-Hillman adduct 1 (3 mmol) in MeCN (4 mL) at r.t. under nitrogen atmosphere. Stirring was continued and the reaction was monitored by TLC. After completion (3-3.5 h), the reaction mixture was quenched with Et2O (25 mL). After the mixture settled, the supernatant organic layer was decanted and the residual semi-solid mass (inorganic part) was further extracted with Et2O. The combined ether extract was washed with brine, dried (Na2SO4), and concentrated to obtain the crude product, which was purified by column chromatography over silica gel to furnish the pure E-alkenone 2. The spectral (IR, 1H NMR and 13C NMR and MS) data of some repesentative adducts and E-alkenones are given bellow.
Compound 1d: IR (KBr): 3474, 1707, 1678, 1442, 1032 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.61 (1 H, dd, J = 8.0, 2.0 Hz), 7.38-7.17 (3 H, m), 6.12 (1 H, s), 5.94 (1 H, d, J = 3.5 Hz), 5.56 (1 H, s), 3.48 (1 H, d, J = 3.5 Hz), 2.75 (2 H, q, J = 7.0 Hz), 1.11 (3 H, t, J = 7.0 Hz). 13C NMR (75 MHz, CDCl3): δ = 203.1, 150.0, 141.8, 128.5, 127.5, 126.8, 125.0, 72.7, 32.0, 8.2. LSIMS (FAB): m/z = 249, 247 [M+ + Na].
Compound 1g: syn:anti = 70:30. IR (KBr): 3418, 1708, 1682, 1463, 1379 cm-1. 1H NMR (300 MHz, CDCl3): δ
(syn) = 6.10 (1 H, s), 5.91 (1 H, s), 4.31 (1 H, t, J = 5.5 Hz), 2.78-2.65 (3 H, m), 1.77-1.52 (3 H, m), 1.12 (3 H, t, J = 7.0 Hz), 0.90 (3 H, t, J = 7.0 Hz), 0.82 (3 H, d, J = 7.0 Hz); δ (anti) = 6.08 (1 H, s), 5.87 (1 H, s), 4.05 (1 H, t, J = 7.0 Hz), 2.78-2.65 (1 H, merged with the signals for anti), 2.38 (2 H, q, J = 7.0 Hz), 1.49-1.33 (3 H, m), 1.12 (3 H, t, J = 7.0 Hz), 0.90 (3 H, t, J = 7.0 Hz), 0.78 (3 H, d, J = 7.0 Hz). 13C NMR (75 MHz, CDCl3): δ (syn) = 202.8, 149.8, 124.7, 75.1, 39.4, 32.0, 26.8, 13.0, 12.1, 8.1; δ (anti) = 203.7, 149.0, 125.0, 77.4, 39.8, 32.0, 24.9, 16.3, 11.9, 8.1. LSIMS (FAB): m/z = 193 [M+ + Na].
Compound 1h: syn:anti = 60:40, IR (KBr): 3418, 1714, 1675, 1460, 1367 cm-1. 1H NMR (300 MHz, CDCl3): δ
(syn) = 6.12 (1 H, s), 5.97 (1 H, s), 4.32 (1 H, d, J = 5.5 Hz), 2.36 (3 H, s), 2.19 (1 H, d, J = 3.5 Hz), 1.72-1.54 (2 H, m), 1.22-1.16 (1 H, m), 0.99-0.87 (6 H, m); δ (anti) = 6.11 (1 H, s), 5.92 (1 H, s), 4.08 (1 H, d, J = 7.0 Hz), 2.36 (3 H, s), 2.19 (1 H, br s), 1.46-1.32 (2 H, m), 1.18-1.07 (1 H, m), 0.85-0.77 (6 H, m). 13C NMR (75 MHz, CDCl3): δ (syn) = 201.0, 150.0, 126.0, 75.1, 39.2, 30.0, 26.9, 14.0, 12.2; δ (anti) = 201.4, 149.8, 126.5, 77.5, 39.8, 30.0, 25.0, 16.5, 12.0. LSIMS (FAB): m/z = 179 [M+ + Na].
Compound 2b: IR (KBr): 1718, 1672, 1462, 1373, 1219 cm-1. 1H NMR (300 MHz, CDCl3): δ = 6.36 (1 H, d, J = 7.0 Hz), 2.70 (1 H, m), 2.68 (2 H, q, J = 7.0 Hz), 1.78 (3 H, s), 1.10-1.02 (9 H, m) Hz). 13C NMR (75 MHz, CDCl3): δ = 202.5, 148.8, 134.7, 30.2, 28.6, 22.4, 11.6, 8.9. LSI-MS (FAB): m/z = 163 [M+ + Na].
Compound 2d: IR (KBr): 1718, 1675, 1630, 1468, 1438, 1363 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.59 (1 H, s), 7.42 (1 H, m), 7.36-7.27 (3 H, m), 2.85 (2 H, q, J = 7.0 Hz), 1.92 (3 H, s), 1.19 (3 H, t, J = 7.0 Hz). 13C NMR (75 MHz, CDCl3): δ = 202.6, 137.8, 135.6, 134.98, 134.92, 130.5, 129.9, 128.2, 126.6, 30.1, 13.8, 8.7. LSIMS (FAB): m/z = 209 [M+ + 1], 211.